The first part of this project will be to identify specific human chromosomal regions containing genes that influence susceptibility to GHD. Linkage analysis searchers for chromosome regions shared by affected individuals in large numbers of families. Will analyze DNA from CHD patients and members of their families in northeastern Quebec, a population with less genetic variation than would be found in cosmopolitan population. This is referred to as a founder effect and can be used to isolate genes. Though the identification of genes should be easier in this Quebec population, the findings will be important for all populations. Computer analyses will allow us to determine chromosomal regions that are common to many of the patients. Finer mapping allows us to determine a relatively smaller region of the chromosome. These candidate regions will contain gene(s) which contribute to the increase in heart disease observed in these families. The second part of this project will be the identification of genes that are located in these regions. Using techniques that comprise "positional cloning," I will physically map the candidate regions and identify specific genes. I have been successful using this technique to isolate the gene responsible for ARSACS, a neurodegenerative disorder found in the same region of Quebec. I will also evaluate genetic variants that have been characterized in other populations using association studies. By conducting these experimental in parallel, I will be able to determine the moderating influence of one gene on another. These two types of analysis, linkage and association, will compliment each other well.